The inability to detect odors is a very real handicap. A diminished sense of smell, which is quite common in the elderly, can lead to malnutrition. A number of medical problems, such as cystic fibrosis and Alzheimer's can cause olfactory dysfunction. Thus it is important to understand the function of the olfactory system. Central to the understanding of the olfactory system is determining how the inputs, the primary olfactory sensory neurons (OSNs), function. Our long-term goal is to understand how olfactory neurons function. Chloride fluxes and intracellular chloride levels are extremely important in determining the ultimate outcome of the exposure of an olfactory neuron to odor. Will the cell be stimulated or inhibited? Chloride levels play an essential role, but because Cl- comes in late in the signal transduction pathway, less attention has be focused on it compared to other second messengers in the transduction pathway. This study will examine the regulation and role of Cl- in olfactory transduction. We will test the hypothesis, that Cl- homeostasis is essential to olfactory neuron function, through the specific aims described below. Aim 1: Characterize [Cl]i under resting and odor simulation conditions The first hypothesis to be tested is that chloride levels will vary among individual olfactory neurons and that the level of intracellular chloride will determine the response of olfactory neurons to CAMP mediated odors. Aim 2: Determine the effects of chloride ion transporters on [CI]i in resting and odor-stimulated neurons. The second hypothesis to be tested is that altering the ion transporters will change the levels of intracellular chloride. Since [Cl]i is unusually high in some olfactory neurons, there must be an active transporter or exchanger(s) that maintains this gradient. Aim 3: Determine the correlation between changes in [Cl]i and electrophysiological responses. The third hypothesis to be tested is that different levels of intracellular chloride will directly affect the type of electrophysiological response of olfactory neurons to odorants.